Neurological emergencies such as stroke, traumatic brain injury, seizures, spinal cord injury, meningitis and others conditions cause significant morbidity and mortality and exact a high cost in terms of human suffering and health care spending. Conducting effective clinical trials in neurological emergencies requires a coordinated network of emergency physicians, neurologists, neurosurgeons, and biostatisticians. This proposal, in response to NINDS RFA NS-06-002, describes the features, functions and coordination we will provide as the Clinical Coordinating Center for the Neurological Emergencies Treatment Trials (NETT) network. The key elements of this structure will include an interdisciplinary team of investigators with specific expertise in the conduct of clinical trials of emergency interventions, a hub-and-spoke network design that acknowledges the importance of enrolling patients in both large academic centers and community hospital emergency departments, and a long term network commitment to advancing the national research infrastructure as it relates to the interdisciplinary study of emergent illness. The first aim of the project is the creation of an optimal network infrastructure for NETT that promotes and conducts high quality, large simple trials. We propose the innovative use of technology to assist in the management, conduct and quality assurance of clinical trials. The operational resources described will enable electronic data entry and automated screening and identification of study participants. The Clinical Coordinating Center will include a Telemedicine Unit and an Outcomes Assessment Unit. A Clinical Translation Unit will assist in designing and conducting trials in a way that facilitates future translation into clinical practice. A second aim is to actively engage clinicians in clinical research and to provide comprehensive and ongoing education for investigators and coordinators. The Education/Training Unit will utilize multimedia materials to provide ongoing training and certification of personnel and ensure optimal protection of human subjects and good research practices. Finally, we describe two clinical trials which demonstrate the capability of NETT. The first is a pre-hospital treatment trial for status epilepticus comparing intramuscular midazolam to intravenous lorazepam for rapid control of seizures in the out-of-hospital setting. The second will be a randomized, double-blind, placebo-controlled trial of ultra-early progesterone in patients with traumatic brain injury. [unreadable] [unreadable] [unreadable]